N-[(4-nitrophenyl)methylideneamino]pyrazine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-[(4-nitrophenyl)methylideneamino]pyrazine-2-carboxamide
• 化学式: C₁₂H₉N₅O₃
• mdl: MFCD01447709
• 分子量: 271.235
• InChiKey: WYNIAZGJCLHKPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(4-nitrophenyl)methylideneamino]pyrazine-2-carboxamide 在 ammonium cerium (IV) nitrate 作用下， 以 neat (no solvent) 为溶剂， 反应 0.33h， 以53%的产率得到2-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine
  参考文献：
  名称：

  Synthesis and spectroscopic study of three new oxadiazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential

  摘要：

  Local reactivity properties and potential for application in new pharmaceutical compounds have been addressed for the three newly synthetized oxadiazole derivatives (2-(5-(2-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHONITRO), 2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METANITRO) and 2(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARANITRO), by application of computational molecular modeling. Within the framework of density functional theory (DFT) this study encompassed calculations of molecular electrostatic potential (MEP), average local ionization energies (ALIE) and bond dissociation energies for hydrogen abstraction (H-BDE). MD simulations have been used in order to assess the influence of water and to identify the atoms of these molecules with preference towards the interaction with water molecules. Molecular docking procedure has been applied in order to check the binding activity of these derivatives against the Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor proteins. The pharmaceutical potential of these derivatives has been assessed by the calculations of the well-established drug likeness parameters. A strong out-of-plane CH mode of the phenyl rings are observed at 769 cm(-1) for ORTHONITRO, 768 cm(-1) for METANITRO and at 848 cm(-1) for PARANITRO in the IR spectrum as expected for substituted benzenes. The VCD signals, corresponding to C=N and NO2 modes of the title compounds are good markers for assigning of absolute configuration. In the title compounds, in ORTHONITRO, the oxadiazole ring is tilted from the phenyl and pyrazine ring while for METANITRO and PARANITRO, there is a planar orientation. The first hyperpolariazabilities of ORTHONITRO, METANITRO and PARANITRO are respectively, 34.83, 54.50 and 174.05 times that of urea. For all the compounds, HOMO is delocalized over the pyrazine and oxadiazole rings, while LUMO is delocalized over whole molecule, except pyrazine ring of ORTHONITRO, over phenyl ring and NO2 group of METANITRO and in the entire molecule of PARANITRO. The title compounds are docked with the proteins, Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor and METANITRO exhibits more inhibitory activity against the receptors than the other ligands. The results obtained from anti-TB activity are more promising as the compounds were found to be more potent than reference standard, ORTHONITRO (MIC = 1.6 mu g/ml), METANITRO (MIC = 0.8 mu g/ml), PARANITRO (MIC = 1.6 mu g/ml), streptomycin (MIC = 6.2 mu g/ml) and pyrazinamide (MIC = 3.1 mu g/ml). (C) 2018 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2018.07.026
• 作为产物：
  描述：

  2-甲酸吡嗪 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 N-[(4-nitrophenyl)methylideneamino]pyrazine-2-carboxamide
  参考文献：
  名称：

  吡嗪-噻唑烷酮杂合支架靶向休眠结核的合成与对接研究

  摘要：

  结核分枝杆菌（MTB）处于休眠期的持久性有助于病原体对当前的抗分枝杆菌药物产生耐药性。为了解决这个问题，我们在本文中报道了通过使用吡嗪和噻唑烯酮支架的分子杂交方法设计的N-（4-氧代-2取代的噻唑烷-3基）吡嗪-2-碳酰肼衍生物的合成。在休眠模型中，针对MTB H37Ra和牛分枝杆菌BCG对化合物进行了评估。大多数化合物的IC 50值在0.3–1μg/ ml范围内。使用MTT测定法进一步测试了活性化合物对THP-1，Panc-1，A549和MCF-7细胞系的抗增殖活性，并且没有显示出明显的细胞毒性。我们还报告了使用活性类似物和MTB-癸烯基磷酸基-β- d-核糖-2'-表异构酶（DprE1）进行的分子对接研究，以合理化生物学活性，并提供有关杂化结构的可能作用机理和结合模式的见解。获得的结果验证了分子杂交方法的使用，并且还表明所报道的化合物可以提供一种新颖的药效团来合成针对dormat MTB的先导化合物。

  DOI：

  10.1016/j.bmcl.2016.03.055

文献信息

• Synthesis and spectroscopic study of three new oxadiazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential
  作者：Y. Sheena Mary、Pankaj B. Miniyar、Y. Shyma Mary、K.S. Resmi、C. Yohannan Panicker、Stevan Armaković、Sanja J. Armaković、Renjith Thomas、B. Sureshkumar

  DOI：10.1016/j.molstruc.2018.07.026

  日期：2018.12

  Local reactivity properties and potential for application in new pharmaceutical compounds have been addressed for the three newly synthetized oxadiazole derivatives (2-(5-(2-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHONITRO), 2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METANITRO) and 2(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARANITRO), by application of computational molecular modeling. Within the framework of density functional theory (DFT) this study encompassed calculations of molecular electrostatic potential (MEP), average local ionization energies (ALIE) and bond dissociation energies for hydrogen abstraction (H-BDE). MD simulations have been used in order to assess the influence of water and to identify the atoms of these molecules with preference towards the interaction with water molecules. Molecular docking procedure has been applied in order to check the binding activity of these derivatives against the Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor proteins. The pharmaceutical potential of these derivatives has been assessed by the calculations of the well-established drug likeness parameters. A strong out-of-plane CH mode of the phenyl rings are observed at 769 cm(-1) for ORTHONITRO, 768 cm(-1) for METANITRO and at 848 cm(-1) for PARANITRO in the IR spectrum as expected for substituted benzenes. The VCD signals, corresponding to C=N and NO2 modes of the title compounds are good markers for assigning of absolute configuration. In the title compounds, in ORTHONITRO, the oxadiazole ring is tilted from the phenyl and pyrazine ring while for METANITRO and PARANITRO, there is a planar orientation. The first hyperpolariazabilities of ORTHONITRO, METANITRO and PARANITRO are respectively, 34.83, 54.50 and 174.05 times that of urea. For all the compounds, HOMO is delocalized over the pyrazine and oxadiazole rings, while LUMO is delocalized over whole molecule, except pyrazine ring of ORTHONITRO, over phenyl ring and NO2 group of METANITRO and in the entire molecule of PARANITRO. The title compounds are docked with the proteins, Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor and METANITRO exhibits more inhibitory activity against the receptors than the other ligands. The results obtained from anti-TB activity are more promising as the compounds were found to be more potent than reference standard, ORTHONITRO (MIC = 1.6 mu g/ml), METANITRO (MIC = 0.8 mu g/ml), PARANITRO (MIC = 1.6 mu g/ml), streptomycin (MIC = 6.2 mu g/ml) and pyrazinamide (MIC = 3.1 mu g/ml). (C) 2018 Elsevier B.V. All rights reserved.
• Synthesis and docking studies of pyrazine–thiazolidinone hybrid scaffold targeting dormant tuberculosis
  作者：T.S. Chitre、K.D. Asgaonkar、P.B. Miniyar、A.B. Dharme、M.A. Arkile、A. Yeware、D. Sarkar、V.M. Khedkar、P.C. Jha

  DOI：10.1016/j.bmcl.2016.03.055

  日期：2016.5

  against current antimycobactrial drugs. To address this issue, we report herein the synthesis of N-(4-oxo-2 substituted thiazolidin-3yl) pyrazine-2-carbohydrazide derivatives designed by following the molecular hybridization approach using pyrazine and thiazolidenone scaffolds. The compounds were evaluated against MTB H37Ra and Mycobacterium bovis BCG in dormancy model. Most of the compounds had IC50

  结核分枝杆菌（MTB）处于休眠期的持久性有助于病原体对当前的抗分枝杆菌药物产生耐药性。为了解决这个问题，我们在本文中报道了通过使用吡嗪和噻唑烯酮支架的分子杂交方法设计的N-（4-氧代-2取代的噻唑烷-3基）吡嗪-2-碳酰肼衍生物的合成。在休眠模型中，针对MTB H37Ra和牛分枝杆菌BCG对化合物进行了评估。大多数化合物的IC 50值在0.3–1μg/ ml范围内。使用MTT测定法进一步测试了活性化合物对THP-1，Panc-1，A549和MCF-7细胞系的抗增殖活性，并且没有显示出明显的细胞毒性。我们还报告了使用活性类似物和MTB-癸烯基磷酸基-β- d-核糖-2'-表异构酶（DprE1）进行的分子对接研究，以合理化生物学活性，并提供有关杂化结构的可能作用机理和结合模式的见解。获得的结果验证了分子杂交方法的使用，并且还表明所报道的化合物可以提供一种新颖的药效团来合成针对dormat MTB的先导化合物。